Tang D, Santella R M, Blackwood A M, Young T L, Mayer J, Jaretzki A, Grantham S, Tsai W Y, Perera F P
Division of Environmental Sciences, Columbia University School of Public Health, New York, New York, USA.
Cancer Epidemiol Biomarkers Prev. 1995 Jun;4(4):341-6.
Polycyclic aromatic hydrocarbon-DNA adducts were measured by ELISA in peripheral leukocytes from 119 non-small cell lung cancer patients and 98 controls at the Columbia-Presbyterian Medical Center. Thirty-one cases had adduct measurements in leukocytes, lung tumor, and nontumor specimens collected at surgery, and 34 had paired leukocyte and tumor specimens. Information on smoking, diet, and occupational exposure was collected. After adjustment for age, gender, ethnicity, season, and smoking, adducts in leukocytes were significantly higher in cases (P < 0.01) than controls; the odds ratio was 7.7 (95% confidence interval = 1.7-34; P < 0.01). Adducts in leukocytes were increased significantly in smokers and ex-smokers compared to nonsmokers among cases and controls (separately and combined) after adjusting for age, gender, ethnicity, and season (P < 0.05). The cases and controls differed in several respects: (a) adducts increased with the number of cigarettes smoked among the 51 cases who were current smokers (P = 0.05) but not among the current smokers in the controls; and (b) a seasonal variation in DNA binding, corresponding to that reported for aryl hydrocarbon hydroxylase inducibility, was observed in cases but not in controls. Among the cases, adducts in leukocytes were correlated more strongly with adducts in the lung tumor tissue than with those in nontumor lung tissue. The results in leukocytes are consistent with a constitutional susceptibility to lung cancer, which results in greater DNA damage from carcinogens in cigarette smoke. They suggested that it may ultimately be possible to use biomarkers such as adducts to identify individuals who would benefit most from early intervention.
在哥伦比亚长老会医学中心，采用酶联免疫吸附测定法（ELISA）检测了119例非小细胞肺癌患者和98例对照者外周血白细胞中的多环芳烃-DNA加合物。31例患者在手术时采集了白细胞、肺肿瘤及非肿瘤标本进行加合物检测，34例患者采集了配对的白细胞和肿瘤标本。收集了有关吸烟、饮食和职业暴露的信息。在对年龄、性别、种族、季节和吸烟情况进行校正后，病例组白细胞中的加合物水平显著高于对照组（P < 0.01）；优势比为7.7（95%置信区间 = 1.7 - 34；P < 0.01）。在校正年龄、性别、种族和季节后，病例组和对照组中吸烟者及既往吸烟者白细胞中的加合物水平均显著高于非吸烟者（分别及合并分析，P < 0.05）。病例组和对照组在几个方面存在差异：（a）在51例现吸烟者中，病例组白细胞加合物水平随吸烟量增加（P = 0.05），而对照组现吸烟者中未观察到这种情况；（b）病例组观察到DNA结合存在季节性变化，与报道的芳烃羟化酶诱导性变化一致，而对照组未观察到。在病例组中，白细胞中的加合物与肺肿瘤组织中的加合物相关性更强，而与非肿瘤肺组织中的加合物相关性较弱。白细胞检测结果与肺癌的先天性易感性一致，这导致香烟烟雾中的致癌物对DNA造成更大损伤。结果表明，最终有可能利用加合物等生物标志物来识别最能从早期干预中获益的个体。
